This invention relates to scintigraphic scanning, and more particularly to organ-specific carriers for technetium-99m.
For some time it has been recognized that conventional organ scanning techniques are not entirely satisfactory for imaging specific body organs. The deficiencies of prior techniques have been generally attributed to the difficulty of preparing a stable radiolabeled diagnostic agent which can be safely delivered to a specific target organ.
In efforts to overcome these deficiencies, a variety of radionuclides have been examined for use as diagnostic agents. Recent interest has been directed toward the use of technetium-99m (.sup.99m Tc) as the preferred radiolabel for diagnostic agents. .sup.99m Tc has been found to be a particularly desirable radionuclide due to its advantageous half-life of about six hours, its adaptability to existing imaging equipment, and its ready commercial availability. It is a general practice to utilize a stable pertechnetate (.sup.99m TcO.sub.4 .sup.-) complex, such as sodium pertechnetate, as a convenient source of .sup.99m Tc. A .sup.99m TcO.sub.4.sup.- solution, in the oxidized pertechnetate form, is obtained, for example, from commercial generators by eluting them with an isotonic saline solution. However, .sup.99m Tc is unique among radionuclides in that as a radiolabel for diagnostic purposes it is generally useful only in its reduced form. Accordingly, carriers suitable for use with the .sup.99m Tc radionuclide must combine with or otherwise provide a reducing agent capable of reducing the pertechnetate ion to its lower valence state.
Recent efforts to provide efficacious radiodiagnostic carriers have been directed toward the use of critically sized particulate materials which, once labeled and administered, are selectively deposited in the specific target organ. For instance, it has been found that submicron particles, on the order of 0.5 to 1 micron, tend to accumulate in the liver while particles on the order of 10 to 100 microns tend to accumulate in the lungs; accordingly, submicron carriers have been used to selectively deliver gamma emitting radionuclides to the liver while larger carriers have been used to deliver radionuclides to the lungs.
In general, a suitable particulate carrier is one which can be easily prepared, is stable, has a narrow range of particle size, is readily radio-labeled, and easily metabolized or discharged by the target organ after diagnostic procedures are complete. Colloids, chelates, and macroaggregates of albumin or polysaccharides have been suggested as particulate radionuclide carriers. For example, U.S. Pat. No. 3,758,678, issued Sept. 11, 1973 to Lindsay, et al. described the preparation of spheroidal biodegradable polysaccharide carrier particles, having critical diameters, selected for their organ specificity.
Although such "sized" carriers provide a general improvement in radionuclide delivery, they are relatively difficult to prepare and are relatively unstable. It has been found that previously suggested particulate carries, when combined with a reduced radionuclide, such as a stannous-technetium complex, form undesirable colloidal aggregates of varying size which are deposited in non-target organs. Thus, the diagnostic accuracy of known particulate carriers is decreased by their combination with the preferred radionuclide. This decrease in accuracy not only reduces the efficacy of the scan, but also results in the exposure of uninvolved organs to radioactive materials.